ES2570744T3 - Derivados (tio)morfolino bisarilo como moduladores S1P - Google Patents
Derivados (tio)morfolino bisarilo como moduladores S1PInfo
- Publication number
- ES2570744T3 ES2570744T3 ES11733829T ES11733829T ES2570744T3 ES 2570744 T3 ES2570744 T3 ES 2570744T3 ES 11733829 T ES11733829 T ES 11733829T ES 11733829 T ES11733829 T ES 11733829T ES 2570744 T3 ES2570744 T3 ES 2570744T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- optionally substituted
- atoms
- fluoro
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36278510P | 2010-07-09 | 2010-07-09 | |
| EP10169108 | 2010-07-09 | ||
| US201161452977P | 2011-03-15 | 2011-03-15 | |
| EP11158269 | 2011-03-15 | ||
| PCT/EP2011/061590 WO2012004375A1 (fr) | 2010-07-09 | 2011-07-08 | Dérivés bisaryl (thio)morpholines modulateurs de s1p |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2570744T3 true ES2570744T3 (es) | 2016-05-20 |
Family
ID=44323383
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11733829T Active ES2570744T3 (es) | 2010-07-09 | 2011-07-08 | Derivados (tio)morfolino bisarilo como moduladores S1P |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US9029371B2 (fr) |
| EP (1) | EP2590954B1 (fr) |
| JP (1) | JP5841593B2 (fr) |
| CN (1) | CN103080096B (fr) |
| AR (1) | AR082137A1 (fr) |
| CA (1) | CA2804329C (fr) |
| DK (1) | DK2590954T3 (fr) |
| ES (1) | ES2570744T3 (fr) |
| MX (1) | MX338605B (fr) |
| PL (1) | PL2590954T3 (fr) |
| TW (1) | TW201206893A (fr) |
| UY (1) | UY33495A (fr) |
| WO (1) | WO2012004375A1 (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI522361B (zh) * | 2010-07-09 | 2016-02-21 | 艾伯維公司 | 作為s1p調節劑的稠合雜環衍生物 |
| TWI543984B (zh) | 2010-07-09 | 2016-08-01 | 艾伯維公司 | 作為s1p調節劑的螺-哌啶衍生物 |
| US8802673B2 (en) * | 2011-03-24 | 2014-08-12 | Hoffmann-La Roche Inc | Heterocyclic amine derivatives |
| MX354815B (es) | 2012-01-12 | 2018-03-22 | Hoffmann La Roche | Derivados heterociclicos como receptores asociados con las aminas traza (taars). |
| CN102670617B (zh) * | 2012-04-13 | 2013-03-20 | 湖南大学 | 布洛芬2-（2-芳基吗啉-4-基）乙酯作为制备抗抑郁药物的应用 |
| US11535632B2 (en) | 2019-10-31 | 2022-12-27 | ESCAPE Bio, Inc. | Solid forms of an S1P-receptor modulator |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1069387A1 (ru) | 1982-07-01 | 1985-11-30 | Институт физико-органической химии и углехимии АН УССР | Дигидрохлорид 5-/ @ -( @ -анизил)- @ -оксиэтил/ 2-(3,4-диметоксифенил)-1-метил-4,5,6,7-тетрагидроимидазо(4,5- @ )пиридина,обладающий спазмолитическим действием |
| GB2228432A (en) | 1989-01-13 | 1990-08-29 | Grayston Central Services | Multi-role machine for heating and coating pipe welds. |
| JPH03206042A (ja) | 1990-01-06 | 1991-09-09 | Takeda Chem Ind Ltd | 降圧剤 |
| JP2681589B2 (ja) | 1992-12-28 | 1997-11-26 | 日揮株式会社 | 配管溶接継手の熱処理方法 |
| JPH072848A (ja) | 1993-04-23 | 1995-01-06 | Sankyo Co Ltd | モルホリンおよびチオモルホリン誘導体 |
| GB9522845D0 (en) | 1995-11-08 | 1996-01-10 | Smithkline Beecham Plc | Novel compounds |
| JP3822680B2 (ja) | 1996-08-30 | 2006-09-20 | 新日本製鐵株式会社 | 誘導加熱された接合部の冷却方法および冷却装置 |
| JP4518587B2 (ja) * | 1998-03-09 | 2010-08-04 | 興和創薬株式会社 | ２−フェニルモルホリン誘導体 |
| MXPA02010325A (es) | 2000-04-21 | 2003-04-25 | Shionogi & Co | Derivados de oxadiazol los cuales tienen efectos anticancer. |
| FR2822727A1 (fr) | 2001-04-03 | 2002-10-04 | Gesal Ind | Procede d'application d'un revetement resistant aux hautes temperatures, dispositif pour la mise en oeuvre de ce procede et objet pourvu dudit revetement |
| JP3649223B2 (ja) | 2003-01-08 | 2005-05-18 | 株式会社日立製作所 | 配管系の熱処理方法および熱処理装置 |
| CA2526209A1 (fr) * | 2003-06-12 | 2004-12-23 | Btg International Limited | Hydroxylamine cyclique en tant que composes psychoactifs |
| US20050090520A1 (en) | 2003-09-12 | 2005-04-28 | Per Lindquist | Treatment of disease or injury of the nervous system with FTY720 |
| US7550485B2 (en) * | 2003-10-14 | 2009-06-23 | Wyeth | Substituted N-heterocycle derivatives and methods of their use |
| GB0329498D0 (en) | 2003-12-19 | 2004-01-28 | Novartis Ag | Organic compounds |
| GB0401332D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| MXPA06012505A (es) | 2004-04-30 | 2006-12-15 | Warner Lambert Co | Compuestos de morfolina sustituida para el tratamiento de trastornos del sistema nervioso central. |
| GB0409744D0 (en) * | 2004-04-30 | 2004-06-09 | Pfizer Ltd | Novel compounds |
| WO2006047195A2 (fr) | 2004-10-22 | 2006-05-04 | Merck & Co., Inc. | Carboxylates, sulfonates, phosphonates, phosphinates 2-(aryl)azacyclylmethyle et heterocycles utilises comme agonistes des recepteurs s1p |
| JP4491334B2 (ja) | 2004-12-01 | 2010-06-30 | 日立Ｇｅニュークリア・エナジー株式会社 | 配管の熱処理方法および装置 |
| JP4599250B2 (ja) | 2005-08-10 | 2010-12-15 | 株式会社東芝 | 高周波誘導加熱時外面温度制御方法および当該制御装置 |
| JP2007063642A (ja) | 2005-09-01 | 2007-03-15 | Hitachi Ltd | 残留応力改善方法と高周波誘導加熱用コイル |
| SG171635A1 (en) | 2006-02-28 | 2011-06-29 | Helicon Therapeutics Inc | Therapeutic piperazines as pde4 inhibitors |
| EP2049548A1 (fr) | 2006-07-27 | 2009-04-22 | UCB Pharma, S.A. | Oxazoles et thiazoles fusionnés en tant que ligands du récepteur histamine h3 |
| KR20090060333A (ko) | 2006-09-08 | 2009-06-11 | 노파르티스 아게 | 림프구 상호작용에 의해 매개되는 질환의 치료에 유용한 ｎ-바이아릴 (헤테로)아릴술폰아미드 유도체 |
| RU2009128062A (ru) | 2006-12-21 | 2011-01-27 | Эбботт Лэборетриз (Us) | Соединения агонисты и антагонисты рецептора сфингозин-1-фосфата |
| AU2008209672B2 (en) * | 2007-02-02 | 2011-02-10 | Novartis Ag | Chromene S1P1 receptor antagonist |
| AU2007227278B2 (en) | 2007-03-21 | 2014-09-11 | Epix Pharmaceuticals, Inc. | SIP receptor modulating compounds and use thereof |
| JP2010525016A (ja) * | 2007-04-23 | 2010-07-22 | ノバルティス アーゲー | Ｓｌｐ受容体調節活性を有するフタラジンおよびイソキノリン誘導体 |
| WO2009084501A1 (fr) | 2007-12-27 | 2009-07-09 | Asahi Kasei Pharma Corporation | Derivé sultame |
| MY150062A (en) | 2008-01-30 | 2013-11-29 | Cephalon Inc | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
| ES2390004T3 (es) | 2008-01-30 | 2012-11-05 | Cephalon, Inc. | Derivados sustituidos de piperidina espirocíclica como ligandos del receptor de la histamina 3(H3) |
| US20090321144A1 (en) | 2008-06-30 | 2009-12-31 | Wyble Kevin J | Protecting an element from excessive surface wear by localized hardening |
| UY32858A (es) * | 2009-08-31 | 2011-03-31 | Abbott Healthcare Products Bv | Derivados de (tio)morfolina como moduladores de sip |
| AR080133A1 (es) | 2010-02-04 | 2012-03-14 | Esteve Labor Dr | Clorhidrato de 4-(-2-((5-metil-1-(2-naftalenil)-1h-pirazol-3-il)oxi)etil)morfolina y formas cristalinas del mismo |
| CN101812058B (zh) | 2010-04-13 | 2012-03-21 | 湖南大学 | 吲哚美辛2-芳基吗啉乙酯及其制备方法与应用 |
-
2011
- 2011-07-07 TW TW100124110A patent/TW201206893A/zh unknown
- 2011-07-08 DK DK11733829.3T patent/DK2590954T3/en active
- 2011-07-08 MX MX2013000361A patent/MX338605B/es active IP Right Grant
- 2011-07-08 CN CN201180033952.8A patent/CN103080096B/zh not_active Expired - Fee Related
- 2011-07-08 WO PCT/EP2011/061590 patent/WO2012004375A1/fr active Application Filing
- 2011-07-08 AR ARP110102456 patent/AR082137A1/es unknown
- 2011-07-08 ES ES11733829T patent/ES2570744T3/es active Active
- 2011-07-08 US US13/808,900 patent/US9029371B2/en not_active Expired - Fee Related
- 2011-07-08 JP JP2013517400A patent/JP5841593B2/ja not_active Expired - Fee Related
- 2011-07-08 PL PL11733829.3T patent/PL2590954T3/pl unknown
- 2011-07-08 EP EP11733829.3A patent/EP2590954B1/fr not_active Not-in-force
- 2011-07-08 UY UY33495A patent/UY33495A/es not_active Application Discontinuation
- 2011-07-08 CA CA2804329A patent/CA2804329C/fr not_active Expired - Fee Related
-
2015
- 2015-03-23 US US14/666,089 patent/US9227960B2/en not_active Expired - Fee Related
- 2015-12-03 US US14/958,382 patent/US9662337B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20160151376A1 (en) | 2016-06-02 |
| US20130203745A1 (en) | 2013-08-08 |
| EP2590954B1 (fr) | 2016-04-13 |
| US9029371B2 (en) | 2015-05-12 |
| US20150191457A1 (en) | 2015-07-09 |
| MX2013000361A (es) | 2013-04-29 |
| CA2804329A1 (fr) | 2012-01-12 |
| DK2590954T3 (en) | 2016-05-02 |
| CN103080096A (zh) | 2013-05-01 |
| UY33495A (es) | 2012-01-31 |
| EP2590954A1 (fr) | 2013-05-15 |
| US9227960B2 (en) | 2016-01-05 |
| MX338605B (es) | 2016-04-22 |
| US9662337B2 (en) | 2017-05-30 |
| CA2804329C (fr) | 2019-05-14 |
| PL2590954T3 (pl) | 2016-09-30 |
| JP2013531003A (ja) | 2013-08-01 |
| TW201206893A (en) | 2012-02-16 |
| JP5841593B2 (ja) | 2016-01-13 |
| AR082137A1 (es) | 2012-11-14 |
| CN103080096B (zh) | 2015-12-09 |
| WO2012004375A1 (fr) | 2012-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2570744T3 (es) | Derivados (tio)morfolino bisarilo como moduladores S1P | |
| PE20230238A1 (es) | Inhibidores de kras g12c | |
| AR108710A1 (es) | Compuestos modulares de fxr (nr1h4) | |
| PE20190336A1 (es) | Nuevos derivados de amonio, un proceso para su preparacion y composiciones farmaceuticas que los contienen | |
| AR089671A1 (es) | 1,4-dihidropirimidinas 4,4-disustituidas y su uso como medicamentos para el tratamiento de la hepatitis b | |
| AR114244A1 (es) | Compuestos que degradan efgr útiles en el tratamiento del cáncer | |
| PE20190656A1 (es) | Compuestos de tiazolo-piridina sustituida como inhibidores de malt1 | |
| AR104963A1 (es) | Derivados de 2-(pirazolopiridin-3-il)pirimidina como inhibidores de jak | |
| AR092045A1 (es) | Combinaciones farmaceuticas | |
| PE20170946A1 (es) | 2-amino-6-(difluorometil)- 5,5-difluoro-6-fenil-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 | |
| AR054127A1 (es) | Imidazoquinolinas como inhibidores de quinasa de lipido | |
| CO6251318A2 (es) | Compuestos heterociclicos de 5 miembros como antagonistas p2x7 | |
| AR110153A1 (es) | ÁCIDOS PROPIÓNICOS 3-SUSTITUIDOS COMO INHIBIDORES DE LA INTEGRINA aV | |
| AR073369A1 (es) | Derivados de 2-carboxamida-cicloamino-urea como inhibidores de pi-3 | |
| CY1119220T1 (el) | Μονοκυκλικο παραγωγο πυριδινης | |
| AR097082A1 (es) | Compuestos terapéuticamente activos y sus métodos de uso | |
| AR089143A1 (es) | Triazolopiridinas sustituidas con actividad inhibidora de ttk | |
| AR101815A1 (es) | Compuestos y composiciones como inhibidores de quinasa | |
| AR095885A1 (es) | Compuestos derivados de arilpirrolopiridina como inhibidores de lrrk2 | |
| AR077695A1 (es) | Derivados de pirimidina como inhibidores del factor ixa | |
| AR117189A1 (es) | Derivados de 6,7-dihidro-4h-pirazolo[1,5-a]pirazin indol-2-carboxamidas activos contra el virus de la hepatitis b (vhb) | |
| PE20141167A1 (es) | Piridopirazinas sustituidas como inhibidores novedosos de ptk | |
| CY1117862T1 (el) | Ετεροκυκλικες ενωσεις βενζοδιοξολιου ή βενζοδιοξεπινης ως αναστολεις φωσφοδιεστερασης | |
| AR095721A1 (es) | Derivados de piridina | |
| AR110282A1 (es) | Compuestos de amida bicíclica y uso de éstos en el tratamiento de enfermedades mediadas por rip1 |